T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes
Autor: | Zhenghong Di, Lei Ma, Li Zhang, Hong-Duo Chen, Xiao-Dong Sun, Ruiqun Qi, Yuxiao Hong, Wei Huo, Xing-Hua Gao, Ya-Ni Lyu |
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Rok vydání: | 2016 |
Předmět: |
Keratinocytes
0301 basic medicine Proteases medicine.medical_treatment Proteinase Inhibitory Proteins Secretory lcsh:Medicine Atopic Dermatitis Filaggrin Proteins Cytokine Filaggrin Lymphoepithelial Kazal-type-related Inhibitor Protease Biology Dermatitis Atopic Interferon-gamma 03 medical and health sciences Th2 Cells Immune system Intermediate Filament Proteins Cell Line Tumor medicine Caspase 14 Humans Cells Cultured Interleukin 4 Interleukin-13 lcsh:R General Medicine Th1 Cells Immunohistochemistry Molecular biology 030104 developmental biology LEKTI Immunology Interleukin 13 Serine Peptidase Inhibitor Kazal-Type 5 Original Article Interleukin-4 |
Zdroj: | Chinese Medical Journal, Vol 129, Iss 3, Pp 295-303 (2016) Chinese Medical Journal |
ISSN: | 0366-6999 |
DOI: | 10.4103/0366-6999.174489 |
Popis: | Background: Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing. Methods: HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry. Results: IL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions. Conclusions: Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes. |
Databáze: | OpenAIRE |
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